SPINAL CORD PLASTICITY MODEL USING NERVE GROWTH FACTOR

本研究的长期目标是开发一种脊柱模型， 使用神经生长因子的脊髓可塑性。 这种神经营养素似乎 选择性地作用于伤害性传入神经， 对皮肤造成伤害的信号。 这些实验将利用 电生理学、解剖学和行为学方法来研究 这种可塑性的各个方面。 几个假设将是 调查，包括a）伤害性传入的可能性， 在出生后关键时期需要NGF， 导致这些传入神经转换为低阈值机械感受器; B）这种转换导致这些神经元的脊柱投射的变化， 传入; c）在NGF治疗的成人中观察到的行为痛觉过敏 脊柱投射系统的变化，特别是那些 涉及某些氨基酸（NMDA）受体;和d）神经的再支配 成年人的伤害感受器需要NGF。 实验设计包括检查 神经生长因子及其抗体对感觉神经元的作用（鉴定 生理学上或解剖学上），对所识别的脊髓神经元， 电路，以及对自然和电气的某些行为反应 刺激. 将用NGF或抗NGF处理的动物与每种动物进行比较。 其他和年龄匹配的未治疗对照。 与卫生有关的 这些实验的重要性来自于需要进一步 关于成人神经系统能力的基本信息， 在受伤后改变其连接性，并记录 天然存在的生物制剂（例如NGF）来调节这一点 可塑性。 此外，NGF是促进再生的候选者。 损伤后的某些神经元类型，有必要确定其 对哺乳动物体内脊髓的功能影响。

The long term objective of this research is to develop a model of spinal cord plasticity using nerve growth factor. This neuronotrophin appears to act selectively on nociceptive afferents that are responsible for signalling damage to the skin. The experiments will make use of electrophysiological, anatomical and behavioural methods to investigate various aspects of this plasticity in rats. Several hypotheses will be investigated, including a) the possibility that nociceptive afferents require NGF in a postnatal critical period and that deprivation from NGF results in conversion of these afferents to low threshold mechanoreceptor; b) that such conversion results in changes in spinal projection of these afferents; c) that behavioural hyperalgesia observed in NGF-treated adults results from changes in spinal projection systems, particularly those involving certain amino acid (NMDA) receptors; and d) that reinnervation of nociceptors in adults requires NGF. Experimental design involves examining the effects of NGF and its antibody on sensory neurons (identified physiologically or anatomically), on identified spinal neurons and circuits, and on certain behavioural responses to natural and electrical stimulation. Animals treated with NGF or anti-NGF will be compared to each other and to age-matched untreated controls. The health-related significance of these experiments derives from the need to have further basic information concerning the capacity of the adult nervous system to modify its connectivity after injury, and to document the ability of naturally-occurring biological agents such as NGF to regulate this plasticity. Furthermore, NGF is a candidate to promote regeneration of certain neuronal types after injury, and it is necessary to ascertain its functional effects on the mammalian spinal cord in vivo.